Discontinuation of Tyrosine Kinase Inhibitor in Children with Chronic Myeloid Leukemia (JPLSG STKI-14 study)

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.25-25
• Main Authors: Shima, Haruko, Kada, Akiko, Tanizawa, Akihiko, Yuza, Yuki, Watanabe, Akihiro, Ito, Masaki, Uryu, Hideko, Koh, Katsuyoshi, Imai, Chihaya, Yoshida, Nao, Koga, Yuhki, Fujita, Naoto, Saito, Akiko M, Adachi, Souichi, Ishii, Eiichi, Shimada, Hiroyuki
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-122623

Background: Tyrosine kinase inhibitor (TKI) has now enabled patients with chronic myeloid leukemia (CML) to live a normal lifespan. However, its long-term side effects such as growth impairment are an issue of concern especially for children. Recent clinical trials in adults have suggested that a subset of CML patients with deep molecular response on TKI therapy may have chance to discontinue TKI without molecular relapse (Saussele et al. Lancet Oncol. 2018). However, the biology of CML in children may differ from adults with more aggressive presentation, and data of TKI discontinuation in CML children are limited (Hijiya et al. Blood. 2019; Bruijn et al. British Journal of Haematol. 2019). Methods: The Japan Pediatric Leukemia/Lymphoma Study Group (JPLSG) CML committee recruited 22 Japanese patients diagnosed with CML-chronic or accelerated phase at < 20 years of age, treated with TKI for ≥ 3 years, and sustained molecular response (MR4.0) for ≥ 2 preceding years. Patients who relapsed after hematopoietic stem cell transplantation (HSCT) were included if total duration of TKI treatment was ≥ 3 years after rejection and relapse, and also met the criteria mentioned above. We prospectively analyzed treatment-free remission rate (TFR) at 12 months. Molecular relapse was defined as at least one loss of major molecular response (MMR), and TKI treatment was restarted as prescribed before discontinuation. Results: All the patients were diagnosed with CML-chronic phase. Median age at diagnosis of CML was 9 years (range, 1 to 14 years), and median age at discontinuation of TKI was 16 years (range, 5 to 26 years). Initial TKI was imatinib in 21 patients, and imatinib was switched to second generation (2G)-TKI in 2 patients because of intolerance or poor response. One patient was treated only with 2G-TKI. Median treatment duration of TKI before discontinuation was 100 months (range, 42 to 178 months), and median duration of MR4.0 was 53.5 months (range, 25 to 148 months). TFR at 12 months was 50.0% (90% CI=31.7-65.8%). Eleven patients experienced molecular relapse and restarted TKI at median of 102 days (range, 67 to166 days) after discontinuation of TKI (Figure. 1). No progression was observed during study, and all 11 patients reachieved MR4.0 at median of 64 days (range, 25 to 196 days) after restart of TKI. All the patients who lost MR4.0 within 3 months after stopping TKI failed to maintain MMR thereafter and restarted TKI. On the other hand, a single patient who